Inclusion body myositis. Genetics, biomarkers and muscle biopsy.
Sporadic inclusion body myositis is the most common idiopathic inflammatory myopathy over the age of 50, with a male-to-female ratio of 3:1. Symptoms onset before age of 60 occurs in 18-20% of patients, with a delay in diagnosis of 5 to 8 years.The classic clinical presentation of SIBM consists of proximal leg and distal arm weakness, and most commonly patients present early slowly progressive quadriceps weakness which leads to falls and to difficulties in climbing stairs, while less common the initial complaints refer to finger flexor weakness and atrophy, foot drop, or dysphagia, and rare presentations include prominent forearm weakness, sparing the quadriceps. The aetiopathogenesis of the disease remains unclear and despite some preliminary promising results, to the day there is no effective treatment.The diagnosis of SIBM is based on the clinical presentation and the histopathological findings in muscle biopsy, however increasing evidence on genetics and paraclinical biomarkers has recently come to light giving new insights on the pathogenesis, the diagnosis and the potential treatment of the disease. In the present study we aim to review the histopathological findings, genetics and blood biomarkers, and to review the role of muscle biopsy in the diagnosis of SIBM.


[Application of fuzzy inference to personal identification--sex determination from teeth].
Fuzzy inference has received much attention recently as a new type of computer control technology for application in various fields. In this study I applied fuzzy inference to personal identification in medical jurisprudence. Sex determination program was constructed from teeth using the fuzzy inference technique and was compared with known discriminant analysis. The materials examined were mandibular and maxillary dental plaster models of 100 adult males and females, and 80 infant males and females. For the permanent teeth, measurements were made on crown width and thickness of the mandibular and maxillary central incisors, canines, first premolars, and first molars, and of the width and length of the maxillary dental arch. For the deciduous teeth, measurements were made on crown width and thickness of all teeth. Stepwise discriminant analysis was conducted using these values. The values from 5 selected upper-ranked items were set as input objects of the fuzzy inference program and the probability of maleness obtained from the discriminant analysis was set as the output object. Finally, sex determination program for both permanent and deciduous teeth was constructed using a fuzzy inference software development tool. Each measured value was input into this program and the output results were compared with those of discriminant analysis. The percentages of correct determinations for permanent teeth were 83.0% for males and 86.0% for females using stepwise discriminant analysis, however it increased to 93.0% for males and 89.0% for females using the fuzzy inference program. The percentages of correct determinations for deciduous teeth models were 67.5% for males and 75.0% for females using stepwise discriminant analysis, and increased to 86.3% for males and 81.3% for females using the fuzzy inference program. Among samples with probabilities between 40% and 60%, 3 out of 14 males and 4 out of 13 females were misjudged using stepwise discriminant analysis in cases of permanent teeth. However using fuzzy inference program, it reduced to 0 for males and 3 for females. In case of deciduous teeth, 9 out of 20 males and 9 out of 23 females were misjudged using stepwise discriminant analysis. But it reduced to 5 for males and 4 for females using the fuzzy inference program.


Effects of Breastfeeding and Formula Feeding on the Expression Level of FTO, CPT1A and PPAR-α Genes in Healthy Infants.
The study aimed to investigate the effect of breastfeeding, formula feeding and mix feeding (breastfed plus formula-fed) on the expression level of obesity-predisposing genes including fat mass and obesity-associated (FTO), carnitine palmitoyltransferase 1A (CPT1A), and peroxisome proliferator-activated receptor-α (PPAR-α) in 5- to 6-month-old infants. A total of 150 infants participated in this case-control study. All subjects were healthy infants aged 5-6 months that divided into 3 groups: breastfed, formula-fed, and mix-fed. The expression level of FTO, CPT1A, and PPAR-α genes in peripheral blood mononuclear cells (PBMC) was evaluated in each group using reverse transcription-polymerase chain reaction (RT-PCR) method. Our findings showed that the current weight, height, and head circumference of infants in the formula feeding and mix feeding groups were significantly higher than those in the exclusive breastfeeding group. The expression level of FTO and CPT1A genes in formula-fed and mix-fed infants was significantly higher (p<0.001) than that in breastfed infants, while the expression level of PPAR-α gene was significantly lower (p<0.05). Breastfeeding showed modulatory effects on the expression level of obesity-predisposing genes and can protect against obesity and subsequent non-communicable diseases. However, more investigations are required to explain the epigenetic effects of breast milk.


Enhancement of Intramolecular Photocycloaddition of Bichromophoric Compounds via Inclusion in Low-Density Polyethylene Films.
The photocycloaddition of tetra- and penta(ethylene glycol) labeled at the chain terminals with 2-naphthoyl groups (N-Pn-N; n = 4 or 5) and tetra(ethylene glycol) terminated by 7-(4-methylcoumarinyl) groups (C-P4-C) has been investigated in hexane solutions and in low-density polyethylene (LDPE) films. At loading levels less than 1 × 10-2 mol/g-film, irradiation of the compounds in LDPE leads to formation of intramolecular photocyclomers to the exclusion of intermolecular products. Irradiations in hexane containing 1 × 10-3 M of a bichromophoric compound produce large amounts of oligomeric material. The difference between the results in solution and the film is explained in terms of the compartmentalization of the guest molecules in the LDPE amorphous regions. Cold-stretching the LDPE films significantly increases the relative efficiency of the intramolecular photocycloadditions due to reduction of the free volume at the reaction sites. This work reports a new approach to synthesize large-ring compounds in high chemical yields at relatively high substrate concentrations.


Effect of renal clearance and continuous renal replacement therapy on appropriateness of recommended meropenem dosing regimens in critically ill patients with susceptible life-threatening infections.
Meropenem plasma concentration above a pathogen's MIC over the whole dosing interval (100% ƒT>MIC) is a determinant of outcome in severe infections. Significant variability of meropenem pharmacokinetics is reported in ICU patients. To characterize meropenem pharmacokinetics in variable CLCR or renal replacement therapy and assess the appropriateness of recommended regimens for MIC coverage. A pharmacokinetic analysis (NONMEM) was conducted with external model validation. Patient characteristics were tested on meropenem clearance estimates, differentiated according to the presence/absence of continuous renal replacement therapy (CRRT, CLCRRT or CLno-CRRT). Simulations evaluated the appropriateness of recommended dosing for achieving 100% fT>MIC in 90% of patients. A total of 101 patients were studied: median 63 years (range 49-70), 56% male, SAPS II 38 (27-48). 32% had a CLCR >60 mL/min, 49% underwent CRRT and 32% presented severe sepsis or septic shock. A total of 127 pathogens were documented: 76% Gram-negatives, 24% Gram-positives (meropenem MIC90 2 mg/L, corresponding to EUCAST susceptibility breakpoint). Three hundred and eighty plasma and 129 filtrate-dialysate meropenem concentrations were analysed: two-compartment modelling best described the data. Predicted meropenem CLno-CRRT was 59% lower in impaired (CLCR 30 mL/min) compared to normal (CLCR 100 mL/min) renal function. Simulations showed that recommended regimens appropriately cover MIC90 in patients with CLCR <60 mL/min. Patients with CLCR of 60 to <90 mL/min need 6 g/day to achieve appropriate coverage. In patients with CLCR ≥90 mL/min, appropriate exposure is achieved with increased dose, frequency of administration and infusion duration, or continuous infusion. Recommended meropenem regimens are suboptimal in ICU patients with normal or augmented renal clearance. Modified dosing or infusion modalities achieve appropriate MIC coverage for optimized antibacterial efficacy in meropenem-susceptible life-threatening infections.


[Epidemiological and financial considerations for the control of Neospora caninum on Swiss dairy farms].
Neospora caninum is widely recognized as one of the most important abortifacients in cattle and causes substantial financial losses to bovine livestock production. This study aimed to calculate the losses caused by N. caninum on Swiss dairy farms and to evaluate the efficacy and profitability of the control strategies culling, not breeding replacements and chemotherapy of calves on farm level. Three different farm sizes with high, medium and low herd prevalences were defined. Epidemiological and financial models were used to simulate the effect of control strategies on the prevalence over time and to perform a cost-benefit analysis. The median annual losses on farm level ranged between CHF 3094.- (= Euro 1875; 60 dairy cattle, high prevalence) and CHF 134.- (= Euro 81; 15 dairy cattle, low prevalence). Culling of animals that had any abortion or a N. caninum abortion, or not breeding replacements from such animals, respectively, were neither effective nor profitable. Only the strategy "not breeding replacements from N. caninum seropositive cows" on farms with a high prevalence was financially attractive. The strategy "chemotherapy of calves" should be re-evaluated as soon as new data regarding the efficacy of treatment and a corresponding protocol have been scientifically validated.


Enzymes of a novel autotrophic CO2 fixation pathway in the phototrophic bacterium Chloroflexus aurantiacus, the 3-hydroxypropionate cycle.
The phototrophic bacterium Chloroflexus aurantiacus can grow autotrophically but seems not to assimilate CO2 via any of the known autotrophic pathways. Holo [Holo, H. (1989) Arch. Microbiol. 151, 252-256] proposed a new pathway in which 3-hydroxypropionate is formed from acetyl-CoA. Previous studies excluded the operation of known CO2 fixation pathways and provided indirect evidence for the suggested pathway based on 13C-labelling experiments. Here all enzyme activities of the postulated cyclic CO2 fixation mechanism are demonstrated in vitro. In essence, acetyl-CoA is carboxylated and reductively converted via 3-hydroxypropionate to propionyl-CoA. Propionyl-CoA is carboxylated and converted via succinyl-CoA and CoA transfer to malyl-CoA. Malyl-CoA is cleaved to acetyl-CoA and glyoxylate. Thereby, the first CO2 acceptor molecule acetyl-CoA is regenerated, completing the cycle and the net CO2 fixation product glyoxylate is released. This cycle represents the fourth autotrophic pathway in nature and is designated the 3-hydroxypropionate cycle.


Occupational exposure to urban stressors and effects on atrial natriuretic peptide: preliminary results.
The aim of this pilot study is to evaluate whether occupational exposure to low doses of pollutants present in the air of the city selected for the study could cause alterations in the concentration of atrial natriuretic peptide (ANP) in workers from the Municipal Police with outdoor tasks, compared to those with indoor tasks. A total of 208 non-smoking male and female subjects were enrolled and divided on the basis of whether their tasks were mainly outdoors or indoors. The dosage of plasma ANP was carried out on all workers included in the study. Differences between means and frequencies were compared using student's t-test for unpaired data and chi-square test with Yates' correction, and they were considered significant when the p value was <0.05. Even after the subdivision of the total sample on the basis of sex, mean plasma levels of ANP were higher but not statistically significant in traffic police compared with controls. The preliminary results suggest that further studies should be conducted before the influence of urban pollution on ANP could be confirmed or rejected.


Structural requirements for the collagenase and elastase activity of cathepsin K and its selective inhibition by an exosite inhibitor.
Human cathepsin K (CatK) is a major drug target for the treatment of osteoporosis. Although its collagenase activity is unique, CatK also exerts a potent elastolytic activity that is shared with human cathepsins V and S. Other members of the cysteine cathepsin family, which are structurally similar, do not exhibit significant collagen and elastin degrading activities. This raises the question of the presence of specific structural elements, exosites, that are required for these activities. CatK has two exosites that control its collagenolytic and elastolytic activity. Modifications of exosites 1 and 2 block the elastase activity of CatK, whereas only exosite-1 alterations prevent collagenolysis. Neither exosite affects the catalytic activity, protease stability, subsite specificity of CatK or the degradation of other biological substrates by this protease. A low-molecular-mass inhibitor that docks into exosite-1 inhibits the elastase and collagenase activity of CatK without interfering with the degradation of other protein substrates. The identification of CatK exosites opens up the prospect of designing highly potent inhibitors that selectively inhibit the degradation of therapeutically relevant substrates by this multifunctional protease.


African ancestry APOE e4 non-carriers with higher educational attainment are resilient to Alzheimer disease pathology-specific blood biomarker pTau181.
Cognitive and functional abilities in individuals with Alzheimer disease (AD) pathology (ADP) show greater than expected variability. While most individuals show substantial impairments in these abilities, a considerable number show little or no impairments. Factors contributing to this variability are not well understood. For instance, multiple studies have shown that higher levels of education are associated with reduced cognitive impairments among those with ADP. However, it remains unclear whether higher levels of education are associated with functional impairments among those with ADP. We studied 410 AA individuals with advanced levels of pTau181 (a biomarker for ADP; individuals as those having log 10 (pTau181) level greater than one standard deviation above the mean) to determine whether EA (categorized as low EA for individuals with ≤ 8 years of education and high EA for those with >8 years) promotes functional resilience and whether this effect varies between APOE ε4 carriers and non-carriers. We used the four non-memory components of the Clinical Dementia Rating (CDR) to create a composite score (CDR-FUNC) to evaluate functional difficulties (scored from 0=no impairment to 12=severe). We employed the non-parametric Mann-Whitney U test to assess the relationship between EA and CDR-FUNC in advanced levels of pTau181 individuals. The results showed that EA promotes resilience to functional problems in AA individuals with advanced levels of pTau181, such that individuals with high EA are more likely to have better functional ability compared to those with lower EA (W=730.5, p=0.0007). Additionally, we found that the effect of high EA on functional resilience was stronger in ε4 non-carriers compared to ε4 carriers (W=555.5, p=0.022). This study extends the role of cognitive reserve and EA to functional performance showing that cognitive reserve influences the association between ADP burden and functional difficulties. Interestingly, this protective effect seems less pronounced in carriers of the strong genetic risk allele ε4. The results highlight the intricate interplay of genetic and non-genetic factors in AD progression, suggesting a need for more personalized strategies to manage functional decline in AD.


Dichotomous sampling of vapor and aerosol of methylene-bis-(phenylisocyanate) [MDI] with an annular diffusional denuder.
A dichotomous sampler was developed for speciation of airborne methylene-bis-(phenylisocyanate) (MDI) into vapor and aerosol fractions. The sampler consisted of an impactor inlet and two sections of annular diffusional denuder, in series with a glass fiber filter. The denuders and filter were coated with N-4-nitrobenzyl-N-1-propylamine for collection and derivatization of MDI followed by high performance liquid chromatography analysis. The sampler was evaluated in the laboratory with test atmospheres of MDI over a range of 24 to 355 micrograms/m3 at an average temperature of 26 degrees C. The total amounts of MDI collected by the dichotomous sampler were not significantly different from a reference sampler over the entire range of MDI concentrations. The first denuder collected MDI vapor with an average efficiency of 91.6 +/- 5.2%, in comparison to a theoretical efficiency of 94.1%. MDI existed solely in the vapor state up to approximately 75 micrograms/m3 and was collected on the denuders. Above this, MDI partitioned into vapor and aerosol, and the device efficiently separated the sample into the vapor fraction, found on the denuders, and the aerosol fraction, which penetrated to the filter. While this work was done with condensation aerosol, appropriate modification of the sampler inlet should allow use of the device for sampling atmospheres containing larger aerosols.


The anaplerotic substrate alanine stimulates acetate incorporation into glutamate and glutamine in rabbit kidney tubules. A (13)C NMR study.
Although acetate, the main circulating volatile fatty acid in humans and animals, is metabolized at high rates by the renal tissue, little is known about the precise fate of its carbons and about the regulation of its renal metabolism. Therefore, we studied the metabolism of variously labeled [(13)C]acetate and [(14)C]acetate molecules and its regulation by alanine, which is also readily metabolized by the kidney, in isolated rabbit renal proximal tubules. With acetate as the sole substrate, 72% of the C-1 and 49% of the C-2 of acetate were released as CO(2); with acetate plus alanine, the corresponding values were decreased to 49 and 25%. The only other important products formed from the acetate carbons were glutamine, and to a smaller extent, glutamate. By combining (13)C NMR and radioactive and enzymatic measurements with a novel model of acetate metabolism, fluxes through the enzymes involved were calculated. Thanks to its anaplerotic effect, alanine caused a stimulation of acetate removal and a large increase in fluxes through pyruvate carboxylase, citrate synthase, and the enzymes involved in glutamate and glutamine synthesis but not in flux through alpha-ketoglutarate dehydrogenase. We conclude that the anaplerotic substrate alanine not only accelerates the disposal of acetate but also prevents the wasting of the latter compound as CO(2).


Second-harmonic dielectric response of an antiferroelectric liquid crystal under dc electric fields.
Second-harmonic dielectric response under dc fields in an antiferroelectric liquid-crystal 4-(1-methyl-heptyloxycarbonyl)phenyl 4-octylcarbonyloxybiphenyl- 4-carboxylate (MHPOCBC) has been investigated. The second-harmonic response from the amplitude mode in the smectic- Calpha* phase was observed due to the symmetry breaking by the application of dc electric fields. A Landau theory was developed in order to analyze experimentally obtained frequency dispersions. From the analysis we found a softening of the amplitude mode with increasing the dc field at a temperature close to the smectic- Calpha*-smectic- A phase transition point. It was turned out that the relaxation frequency of the amplitude mode decreases linearly with the applied electric field.


Case reports and their importance in Medical Literature.
It is important to appreciate how case reports have paved the way for modern research. They are still largely considered the first line of evidence. Indeed global endemics such as HIV and Zika Virus have been traced back to initial case reports. Strictly speaking; case reports are anecdotes - a factual story telling about nature's own experiment. Case reports can be characterized by two huge advantages, their ability to present novel, rare cases in a manner that can lead to the expansion in research of such cases and their use in generating new, innovative hypothesis that can be used to direct further research. The aim of this article is to identify the place and purpose of case reports in the current research setting with a focus on highlighting its merits and limitation amongst other things.


New evidence supporting the linkage to extracellular space of outer segment saccules of frog cones but not rods.
Previous electron microscopic examinations of outer segments of photoreceptors suggest that many flattened saccules of cones are continuous with the cell membrane and that their lumina connect with the extracellular compartment but that most saccules in rods appear to lack these connections. The saccules probably contain photolabile pigment, and certain potentials appear to result from dipole formation during pigment bleaching. The detection of dipoles from rod saccules may require that the lumina of rod saccules connect with extracellular space, and questions have been raised whether the interpretation of micrographs is correct or the isolation of rod saccules is the result of artifact. Accordingly, lanthanum and barium precipitates were produced near fixed and unfixed frog photoreceptors. Lanthanum precipitates appeared to infiltrate the saccules of fixed cones and the few surviving cones exposed prior to fixation, but no rod saccules were infiltrated except occasional, most basal saccules or saccules within narrow zones of probable damage. Barium precipitates did not infiltrate saccules of either variety of unfixed photoreceptor, but they did occasionally infiltrate around the saccules at points of damage in rod outer segments. The results thus support the view of the patency of saccules of frog cones and are consistent with, but do not prove, the isolation of saccules of frog rods.


Training-induced recovery of manual dexterity after a lesion in the motor cortex.
Cerebral injury, such as stroke, cause functional deficits; however some functions can recover with postlesion rehabilitative training. Several recent studies using rodents and monkeys have reported the effects of postlesion training on functional recovery after brain injury. We present herein an overview of recent animal experimental studies on the effects of postlesion motor training on brain plasticity and motor recovery. Our study in the macaque monkey reported the effects of hand motor training on motor recovery after lesioning of the primary motor cortex (M1). In monkeys that had undergone intensive daily training after the lesion, manual dexterity recovered to previous levels. Relatively independent digit movements, including those of precision grip, were restored in the trained monkeys. While hand movements recovered to some extent in the monkeys without postlesion training, these monkeys frequently used alternative grips to grasp a small object instead o f the precision grip. These findings suggest that recovery after M1 lesions includes both training-dependent and training-independent processes, and that recovery of precision grip requires intensive postlesion training. Recent results of both brain imaging and gene expression analyses suggest that functional and structural changes may occur in uninjured motor areas during recovery of hand function after M1 lesions. In particular, our preliminary results suggest that structural changes in ventral premotor cortex neurons may participate in functional compensation of precision grip.


Identification and characterization of a methionine γ-lyase in the calicheamicin biosynthetic cluster of Micromonospora echinospora.
CalE6 is a previously uncharacterized protein involved in the biosynthesis of calicheamicins in Micromonospora echinospora. It is a pyridoxal-5'-phosphate-dependent enzyme and exhibits high sequence homology to cystathionine γ-lyases and cystathionine γ-synthases. However, it was found to be active towards methionine and to convert this amino acid into α-ketobutyrate, ammonium, and methanethiol. The crystal structure of the cofactor-bound holoenzyme was resolved at 2.0 Å; it contains two active site residues, Gly105 and Val322, specific for methionine γ-lyases. Modeling of methionine into the active site allows identification of the active site residues responsible for substrate recognition and catalysis. These findings support that CalE6 is a putative methionine γ-lyase producing methanethiol as a building block in biosynthesis of calicheamicins.


Delivery strategies for treatment of age-related ocular diseases: From a biological understanding to biomaterial solutions.
Age-related ocular diseases, such as age-related macular degeneration (AMD), diabetic retinopathy, and glaucoma, result in life-long functional deficits and enormous global health care costs. As the worldwide population ages, vision loss has become a major concern for both economic and human health reasons. Due to recent research into biomaterials and nanotechnology major advances have been gained in the field of ocular delivery. This review provides a summary and discussion of the most recent strategies employed for the delivery of both drugs and cells to the eye to treat a variety of age-related diseases. It emphasizes the current challenges and limitations to ocular delivery and how the use of innovative materials can overcome these issues and ultimately provide treatment for age-related degeneration and regeneration of lost tissues. This review also provides critical considerations and an outlook for future studies in the field of ophthalmic delivery.


Fast fabrication of a hybrid monolithic column containing cyclic and aliphatic hydrophobic ligands via photo-initiated thiol-ene polymerization.
Three monomers, octakis (3-mercaptopropyl) octasilsesquioxane, 1,2,4-trivinylcyclohexane and isophytol were employed to synthesize a novel monolithic stationary phase via photo-initiated thiol-ene click polymerization for reversed-phase liquid chromatography. Several factors such as porogenic system, reaction time and the molar ratio of functional groups were investigated in detail. The resulting poly(POSS-co-TVCH-co-isophytol) monolithic column exhibited suitable permeability for fast separation and outstanding thermal stability. Five alkylbenzenes were employed to evaluate the ability of chromatographic separation of the resulting monolithic columns at different flow rates, and showed the highest column efficiencies of 90,200-93,100 N/m (corresponding to 10.4-10.6 μm of plate height) at a velocity of 0.41 mm/s. The baseline separations of five anilines and eight phenols further proved the applicability of poly(POSS-co-TVCH-co-isophytol) monolithic column in the separation of small molecules.


Statistical association between cancer incidence and major-cause mortality, and estimated residential exposure to air emissions from petroleum and chemical plants.
An ecologic study design was used to investigate the relationship between exposure to air emissions produced by the petroleum and chemical industries, and average annual cancer incidence and major cause mortality rates among whites in Contra Costa County, California. Estimates for the exposure to major industrial sources of sulfur dioxide, hydrocarbons and oxides of nitrogen were used to subdivide the county by level of exposure to petroleum refinery and chemical plant emissions. Cancer incidence and major cause mortality rates were then calculated for whites in each of the exposure areas. In both males and females, residential exposure to petroleum and chemical air emissions was associated with an increased incidence of cancer of the buccal cavity and pharynx. In males, age-adjusted incidence rates for cancers of the stomach, lung, prostate and kidney and urinary organs were also associated with petroleum and chemical plant air emission exposures. In both sexes, we found a strong positive association between degree of residential exposure and death rates from cardiovascular disease and cancer, and a less strong positive association between exposure and death rates from cerebrovascular disease. There was also a positive association in men for deaths from cirrhosis of the liver. Although these observed associations occurred across areas of similar socioeconomic and broad occupational class, confounding variables and the "ecologic fallacy" must be considered as possible explanations. In particular, the stronger findings in men suggest an occupational explanation of the cancer incidence trends, and the effect observed in cirrhosis mortality suggests that lifestyle variables such as alcohol consumption were not adequately controlled for. While the public health implications of our findings remain unclear, the evidence presented is sufficient to warrant follow-up studies based on individual data in which possible biases can be more readily controlled.


A Pilot Study of Palliative Care Provider Self-competence and Priorities for Education in Kenya.
This study explored palliative care provider self-competence and priorities for future education in an inpatient hospice setting in Kenya. Self-competence scores for clinical skills and patient and family communication skills were hypothesized to differ according to provider type. A descriptive, cross-sectional study design was piloted at Kimbilio Hospice, a 26-bed rural, inpatient facility in Kenya. A quantitative survey instrument entitled, "Self assessment of clinical competency and concerns in end-of-life care," was administered to participants. Survey responses were collected from 5 clinical staff, 11 caregivers, and 8 support staff. Data were analyzed using Kruskal-Wallis test to compare between mean scores. Statistically significant differences were found in 5 self-competence variables: performing a basic pain assessment, use of oral opioid analgesics, assessment and management of nausea/vomiting and constipation, and discussing an end-of-life prognosis with a patient's family member (P < .05). Sixteen participants (66%) selected pediatric palliative care as their top priority for future education. The findings support the hypothesis that palliative care providers have varying levels of self-competence. Improving education to build palliative care competencies in adult and pediatric palliative care in sub-Saharan Africa is recommended.


[Development of arterial pressure rhythm and cardiac contraction rate and effects of beta-adrenomimetic agents].
Blood pressure (BP) and heart rate (HR) rhythms were studied in premature infants (299 profiles ranged 24-106 h at 20--min intervals) and 11-13-year-old children (19 profiles for 48 h at 15-min intervals) to explore ultradian-to-circannual rhythm characteristics in BP and HR in preterm human infant and to elucidate the influence of antenatal betamimetic (BM) exposure on adolescent BP and HR rhythms. A circannual modulation of the 3-h amplitude (A) or MESOR of systolic BP (SBP) and diastolic BP (DBP) was seen mainly in prematures with a positive family history of high BP on the father's (f+) side or with both a patro linous and matro-linous history (f+m+), the circannual modulation of HR ultradian A was statistically significant only in "f- m-" infants. In urine collected at 3 h intervals for 24-h spans from 21 premature infants Na+,K+ and 11-oxycorticosteroids had a significant circadian rhythm. 9 adolescents (BM+), which were exposed in utero to different BM doses, had a significantly higher SBP and DBP MESOR and numerically higher circadian A as compared to 10 controls (BM-); correlation (P less than 0.05) between BM dose and HR circadian A was found. DBP led SBP in 8 or 10 "BM-" but in 4 of 9 "BM+" (acrophase difference 17 min and 3 min correspondingly).(ABSTRACT TRUNCATED AT 250 WORDS)


The cross-species A3 adenosine-receptor antagonist MRS 1292 inhibits adenosine-triggered human nonpigmented ciliary epithelial cell fluid release and reduces mouse intraocular pressure.
Antagonists to A3 adenosine receptors (ARs) lower mouse intraocular pressure (IOP), but extension to humans is limited by species variability. We tested whether the specific A3AR antagonist MRS 1292, designed to cross species, mimicks the effects of other A3AR antagonists on cultured human nonpigmented ciliary epithelial (NPE) cells and mouse IOP. NPE cell volume was monitored by electronic cell sorting. Mouse IOP was measured with the Servo-Null Micropipette System. Adenosine triggered A3AR-mediated shrinkage of human NPE cells. Shrinkage was blocked by MRS 1292 (IC50 = 42 +/- 11 nM, p < 0.01) and by another A3AR antagonist effective in this system, MRS 1191. Topical application of the A3AR agonist IB-MECA increased mouse IOP. MRS 1292 reduced IOP by 4.0 +/- 0.8 mmHg at 25-microM droplet concentration (n = 10, p < 0.005). MRS 1292 inhibits A3AR-mediated shrinkage of human NPE cells and reduces mouse IOP, consistent with its putative action as a cross-species A3 antagonist.


[Biomechanical effects of iliac screw plates on stability of lumbo-iliac fixation construct].
To evaluate the biomechanical effect of a self-made iliac screw plate on the stability of lumbo-iliac fixation construct before and after fatigue loading. Twelve fresh lumbo-pelvic specimens from donated adult cadavers with formalin embalm were used in the study. According to whether use the iliac screw plate or not, the specimens were randomly assigned into group A (with iliac screw plate, n=6) and group B (without iliac screw plate, n=6). The bone mineral density (BMD) of L(t-4) was measured using dual-energy radiograph absorptiometry. The pedicle screw and iliac screw fixation were given at L3-5, and bilateral facetectomy and diskectomy at L5, S1 level were performed to prepare the model of the intervertebral destabilization. The biomechanical testing was conducted on a material testing machine under 0-600 N compression and -7-7 N.m torsion loading modes for the initial compressive stiffness and torsional stiffness evaluation. And then 20 000 cyclic compressive loading of 40-400 N was given to the specimen, the stiffness evaluation was repeated. Then the maximum pull-out strength of screws at every level was measured and compared. Gross observation and radiological observation were performed during experiment. The BMD values of groups A and B were (1.15 +/-0.13) g/cm(2) and (1.12 +/-0.11) g/cm(2) respectively, showing no significant difference between 2 groups (t=0.428, P=0.678). All pedicle screws and iliac screws were inserted in good position; no loosening or breaking of screw was observed during loading. After fatigue loading, the incidence of halo ring around the iliac screws of groups A and B was 16.7% (1/6) and 50.0% (3/6), respectively. The compressive stiffness and torsional stiffness after fatigue loading were significantly lower than those in initial state in groups A and B (P < 0.05); there was no significant difference in compressive stiffness and torsional stiffness between groups A and B before fatigue loading (P > 0.05). However, group A had higher compressive stiffness than group B (t=2.664, P=0.024) after fatigue loading, and there was no significant difference in torsional stiffness between 2 groups (t=0.410, P=0.690). No significant difference was found in screw pull-out strength of pedicle screws at L3, L4, and L5 levels between groups A and B (P > 0.05); however, the pull-out strength of the iliac screws in group A was significantly higher than that in group B (t=3.398, P=0.007). In groups A and B, the pull-out strength of L3 screw was significantly lower than that of L4 and L5 screws (P < 0.05). In group A, pull-out strength of the iliac screws was significantly higher than that of L3, L4, and L5 screws (P < 0.05); in group B, the pull-out strength of iliac screws was significantly lower than that of L4 and L5 screws (P < 0.05). In the lumbo-iliac reconstruction, the use of iliac screw plate could resist iliac screw loosening, therefore, it has the potential to increase the stability oflumbo-iliac fixation construct.


The effects of horseback riding participation on the muscle tone and range of motion for children with spastic cerebral palsy.
The objective of this research is to verify the effects of horseback riding participation on the muscle tone of pelvic limbs and articular range of motion for children with spastic cerebral palsy. The research target is 16 children with spastic cerebral palsy, 8 children for the experimental group and 8 children for the control group. As a tool to measure the muscle tone, Modified Ashworth Scale (MAS), was used and a goniometer was used to measure the range of motion (ROM). A therapeutic horseback riding program was conducted to an experimental group of 8 children with spastic cerebral palsy in the therapeutic horseback riding for 60 min a day, 2 days a week and a total of 12 weeks. The results are as follows: First, the participation in the therapeutic horseback riding program showed a statistically significant difference in the muscle tone for the knee of children with spastic cerebral palsy (P< 0.01). Second, though the difference in knee muscle tone between the experimental group and the control group was statistically insignificant, the average was improved by the participation. Third, the participation in the therapeutic horseback riding program showed a statistically significant difference in the hip-joint motion range for the knee of children with spastic cerebral palsy (P< 0.01). Fourth, though the difference in the hip joint motion range between the experimental group and the control group was statistically insignificant, the average was improved by the participation.


Methodological issues in trials assessing primary prophylaxis of venous thrombo-embolism.
Many trials have been conducted to assess the efficacy of various strategies in the prevention of venous thrombo-embolism (VTE). Some of these trials have been subject to methodological criticisms. We aimed to assess the methodological issues raised by VTE trials. We searched MEDLINE and the Cochrane Central Register of Controlled Trials for articles assessing primary thromboprophylaxis published between 1994 and 2003 in 60 general medical and specialty journals. A total of 77 articles were analysed by two independent reviewers using a list of items. No primary endpoint was defined in 20% of trials. Although the primary endpoint was collected before day 15 in 75% of trials, there were >/=20% missing data in 56% of articles and >/=30% in 24.2% of articles. The rate of missing data was 23.7+/-9.7% in studies using venography-detected deep-vein thrombosis as an endpoint compared with 5.6+/-6.0% in studies using other endpoints. Among the 47 superiority trials, 27 (57.4%) reported an intention-to-treat (ITT) analysis, but only 10 (21.3%) reported an analysis that complied with this principle. These results were consistent when limiting the analysis to articles published in high-impact journal (impact factor more than 5). Recent randomized controlled trials assessing prophylactic regimens in VTE have important methodological limitations in terms of primary endpoints, missing data, and compliance with the ITT principle. These methodological shortcomings should be addressed when planning future trials.


Trajectory of the COVID-19 pandemic: chasing a moving target.
The spread of COVID-19 has already taken a pandemic form, affecting over 180 countries in a matter of three months. The full continuum of disease ranges from mild, self-limiting illness to severe progressive COVID-19 pneumonia, multiorgan failure, cytokine storm and death. Younger and healthy population is now getting affected than before. Possibilities of airborne and fecal oral routes of transmission has increased the concern. In the absence of any specific therapeutic agent for coronavirus infections, the most effective manner to contain this pandemic is probably the non-pharmacological interventions (NPIs). The damage due to the pandemic disease is multifaceted and crippling to economy, trade, and health of the citizens of the countries. The extent of damage in such scenarios is something that is beyond calculation by Gross Domestic Product rate or currency value of the country. Unfortunately, unlike many other diseases, we are still away from the target antiviral drug and vaccine for severe acute respiratory syndrome (SARS-CoV-2) infection. The prime importance of NPIs like social distancing, staying in home, work from home, self-monitoring, public awareness, self-quarantine, etc. are constantly being emphasized by CDC, WHO, health ministries of all countries and social media houses. This is time of introspection and learning from our mistakes. Countries like China and South Korea who were initially the most hit countries could contain the disease spread by liberal testing of their population, stringent quarantine of people under investigation and isolation of the positive cases. Rest of the countries need to act urgently as well to bring an immediate halt in the community transmission.


Evaluation of a tactile breath pacer for sleep problems: A mixed method pilot study.
Sleep problems, like insomnia, are a prevalent condition associated with major health risks. Prevention and treatment of sleep problems are thus essential to preserve physical and mental health. Previous work supports the effectiveness of breathing guidance for sleep problems and recommends breathing exercises as an effective intervention for insomnia. While new technologies can support breathing guidance, such novel devices should be assessed for effectiveness and usability to facilitate implementation and continued use. The current pilot study investigates the acceptability and usability of a mobile tactile breathing device and explores its potential impact on subjective sleep quality. In this mixed-method pilot study, 39 participants tested the breathing device for one month in naturalistic circumstances. We collected their experiences, subjective sleep quality, and feedback regarding the usability of the device and the accompanying app through a survey in a pre-post design. The results show that the breathing device is an acceptable solution for sleep problems and participants particularly appreciate the standalone function and design. Nevertheless, important points of attention, such as the size of the device, were also identified. Explorative analyses suggest that subjective sleep quality improved after using the device and accompanying app. The current study supports the usability and acceptability of a tactile breath pacer and provides preliminary evidence supporting a positive impact of the technology on the sleep quality of participants. Recommendations for developers of breathing technologies and eHealth are devised based on the findings.


It is time to rethink juvenile idiopathic arthritis classification and nomenclature.
Juvenile idiopathic arthritis (JIA) is not a disease, but an exclusion diagnosis that encompasses all forms of arthritis that begin before the age of 16 years, persist for more than 6 weeks, and are of unknown origin. This heterogeneous group of chronic arthritides has been classified on clinical and laboratory grounds to try to identify homogeneous, mutually exclusives categories suitable for etiopathogenic studies . Recent advances have shown that while some JIA categories identify quite definite disease entities, others still include heterogeneous conditions. Some aspects of JIA classification and nomenclature need therefore to be reconsidered.


Association of Quality of Coronal Filling with the Outcome of Endodontic Treatment: A Follow-up Study.
The aim of this study was to assess the effect of the quality of the coronal restoration and the root filling on the success of endodontic treatment. Patients treated at Kuwait University Dental Clinics (KUDC) from 2003 to 2014 were contacted by telephone calls. Demographic data and clinical records of patients, including age, gender, the tooth number, and medical history were recorded. Each patient received clinical examination for all teeth, including assessment of the coronal filling (type, quality), root- and/or coronal fracture, and the periodontal condition around the tooth (e.g., probing depth, gingival recession); percussion and mobility tests. A periapical radiograph of the endodontic treated tooth was taken to determine the health of the periapical tissues using the periapical index. The quality of the root filling was assessed by length and density of the root filling. The mean follow-up period was 4.8 years. The overall success rate of endodontic treatment was 86%; teeth without any initial periapical lesion had a success of 93%, whereas those with such lesion had a success rate of 80%. Periapical healing was not significantly associated with either the length of root filling (p = 0.40) or the density of root filling (p = 0.099), but was statistically significantly associated with the presence of coronal filling defects (p = 0.001). This study demonstrated that inadequate coronal filling but not the quality of root filling was associated with a higher prevalence of periapical lesions.


Dynamic Modeling of CHO Cell Metabolism Using the Hybrid Cybernetic Approach With a Novel Elementary Mode Analysis Strategy.
Chinese hamster ovary (CHO) cell culture has a major importance on the production of biopharmaceuticals, including recombinant therapeutic proteins such as monoclonal antibodies (MAb). Mathematical modeling of biological systems can successfully assess metabolism complexity while providing logical and systematic methods for relevant genetic target and culture parameter identification toward cell growth and productivity improvements. Most modeling approaches on CHO cells have been performed under stationary constraints, and only a few dynamic models have been presented on simplified reaction sets, due to substantial overparameterization problems. The hybrid cybernetic modeling (HCM) approach has been recently used to describe the dynamic behavior by incorporating regulation between different metabolic states by elementary mode participation control, with sets of equations evaluated by objective functions. However, as metabolic networks evaluated are constructed toward a genomic scale, and cell compartmentalization is considered, identification of the active set becomes more difficult as EM number exponentially grows. Thus, the development of robust approaches for EM active set selection and analysis with smaller computational requirements is required to impulse the use of cybernetic modeling on larger up to genome-scale networks. In this report, a novel elementary mode selection strategy, based on a polar representation of the convex solution space is presented and coupled to a cybernetic approach to model the dynamic physiologic and metabolic behavior of CHO-S cell cultures. The proposed Polar Space Yield Analysis (PSYA) was compared to other reported elementary mode selection approaches derived from Common Metabolic Objective Analysis (CMOA) used in Flux Balance Analysis (FBA), Yield Space Analysis (YSA), and Lumped Yield Space Analysis (LYSA). For this purpose, exponential growth phase dynamic metabolic models were calculated using kinetic rate equations based on previously modeled growth parameters. Finally, complete culture dynamic metabolic flux models were constructed using the HCM approach with selected elementary mode sets. The yield space elementary mode- and the polar space elementary mode- hybrid cybernetic models presented the best fits and performances. Also, a flux reaction perturbation prediction approach based on the polar yield solution space resulted useful for metabolic network flux distribution capability analysis and identification of potential genetic modifications targets.


Left ventricular diastolic dysfunction is related to oxidative stress and exercise capacity in hypertensive patients with preserved systolic function.
Left ventricular diastolic dysfunction and oxidative stress are important determinants in heart failure development. Peak oxygen uptake, maximal oxygen consumption, metabolic equivalents (MET), ventilatory response and time to respiratory gas exchange assess cardiopulmonary capacity. It was the aim of this study to investigate the impact of oxidative stress on diastolic indexes and cardiopulmonary exercise capacity in hypertensive patients with left ventricular diastolic dysfunction. Mitral flow velocities (E, A), ejection fraction, left atrial and ventricular diameters were assessed by Doppler echocardiography. Superoxide dismutase (SOD) and glutathione peroxidase activity in blood were evaluated. Sixty patients (aged 49.8 +/- 9.2 years) with essential hypertension and preserved systolic function (ejection fraction 58.3 +/- 7%) performed a bicycle exercise test. Forty patients showed impaired left ventricular relaxation (E/A <1, deceleration time of E >220 ms) and were assigned to group 1, while 20 had normal relaxation (group 2). An increase in SOD was significantly blunted after exercise in group 1 compared with group 2 (p = 0.049). A significant difference between groups in the glutathione peroxidase level was observed before exercise (p = 0.038). There were significantly lower values of peak oxygen uptake and MET (p = 0.013 and p = 0.024, respectively) and a prolonged respiratory exchange ratio (p = 0.022) in group 1 compared with group 2. MET was significantly influenced by SOD level (p = 0.035). Lower antioxidative protection and impaired relaxation decrease cardiopulmonary capacity in hypertensive patients.


TREATMENT OF PULMONICOLA COCHLEOTREMA INFECTION WITH IVERMECTIN-PRAZIQUANTEL COMBINATION IN AN ANTILLEAN MANATEE (TRICHECHUS MANATUS MANATUS).
The aim of this study was to report the use of an oral combination of ivermectin plus praziquantel in the treatment of a Pulmonicola cochleotrema in an Antillean manatee ( Trichechus manatus manatus). A female manatee was found exhibiting respiratory changes and the presence of parasites in the nares. Based on clinical manifestations presented by the manatee, a symptomatic therapeutic protocol was employed, which included an anthelmintic treatment using a combination of ivermectin plus praziquantel. The parasites retrieved were identified as P. cochleotrema. The fourth day after the onset of the therapeutic protocol, the clinical signs declined and on the seventh day posttreatment no clinical signs were observed. This is the first time a therapeutic protocol of ivermectin plus praziquantel has been used in the treatment of P. cochleotrema in manatees.


Association of pre-operative medication use with unplanned 30-day hospital readmission after surgery in oncology patients receiving comprehensive geriatric assessment.
This study aimed to determine whether pre-operative medication use is associated with unplanned 30-day readmission in elderly people undergoing cancer surgery. Patients aged 65 years or older who were scheduled for cancer surgery and presented for comprehensive geriatric assessment were included. Comparisons of variables between patients with readmission and those without readmission were performed by univariate and multivariate analyses. A total of 473 patients were included. Multivariate analysis showed that pre-operative discontinuation-requiring medications (PDRMs) and gastrointestinal/hepato-pancreato-biliary (GI/HPB) cancer were significant factors for 30-day readmission. PDRM increased the risk of readmission by about 2.2-fold. Attributable risk of PDRM to readmission was around 55%. The adjusted odds ratio and attributable risk for GI/HPB surgery was 3.4 (95% CI 1.0-11.5) and 70.8%, respectively. Medication use has an impact on unplanned 30-day readmission in geriatric oncology patients, further highlighting the importance of medication optimization for elderly patients with cancer surgery.


Lamb wave acousto-optic modulator in ZnO/MgO multiple quantum wells and comparison with classical modulator.
An analysis of a ZnO/MgO multiple quantum well (MQW) acousto-optic modulator with Lamb waves is performed. With the MQW thickness in the range of 0.2 times the Lamb wavelength, the only observed Lamb modes are the lowest-order symmetric S0 and antisymmetric A0 modes. These modes induce strain and electric field components which influence the absorption coefficient of the modulator by the associated variation of the excitonic energies of MQW. The optical absorption coefficient spectra of the modulator as a function of the Lamb waves' power is presented. The Lamb-wave-based modulator gives a better absorption coefficient than the Rayleigh-wave-based one. An analysis of a classical acousto-optic modulator is also performed for comparison of performance.


[Analysis of a pedigree affected with propionic acidemia by trio whole exome sequencing].
To explore the clinical characteristics and genetic basis for a pedigree affected with propionic acidemia. Trio whole exome sequencing (WES) was used to screen potential variants in the proband and his parents. Sanger sequencing was carried out for the elder sister of the proband, and prenatal diagnosis was carried out at 18th gestational week upon the next pregnancy of his mother. Two novel heterozygous variants, PCCA c.1845+1G>A and c.446delA, were detected by WES, for which his father and mother were respectively heterozygous carriers. His elder sister also inherited the PCCA c.1845+1G>A variant from her father, while the fetus was heterozygous for the PCCA c.1845+1G>A variant. Above results were confirmed by Sanger sequencing. Identification of the PCCA c.1845+1G>A and c.446delA variants by WES has facilitated genetic counseling and prenatal diagnosis for this family.


Concentration and relationship to progesterone of progesterone-binding globulin in pregnant guinea-pigs: measurement by progesterone tracer binding assay.
A single-point progesterone tracer binding assay (TBA) was developed to measure the concentration of progesterone-binding globulin (PBG) in the serum of pregnant guinea-pigs. Tritiated progesterone was added to dilutions of a reference serum, the percentage bound calculated and a standard curve constructed. The amount of progesterone tracer bound to serum samples was determined, and the concentration of binding protein in the sample relative to the reference was calculated. The molar concentration in the reference serum was determined by Scatchard analysis. The TBA could readily process 30 samples per day. There was a rapid rise in PBG concentrations between days 15 and 20 of gestation, in parallel with progesterone concentrations. The molar ratio of PBG: progesterone was approximately 10:1 after this time, until about day 45 when there was an increase in ratio.


[Mitral valve plasty through right thoracotomy with submammary skin incision].
A 30-year-old female with congestive heart failure was referred to our hospital and massive mitral regurgitation was detected on the echocardiography. She was a mother of 2 infants, and wished early recovery from surgery, cosmetic consideration to skin incision and future pregnancy. Her mitral valve was successfully repaired through right thoracotomy with submammary skin incision. Postoperative transthoracic Doppler echocardiography revealed no mitral regurgitation. The patient recovered uneventfully and was discharged on the 8th postoperative day. And she has been drug-free since then.


[Clinical research activity of the French cancer cooperative network: Overview and perspectives].
The French Cancer Plan 2014-2019 stresses the importance of strengthening collaboration between all stakeholders involved in the fight against cancer, including cancer cooperative groups and intergroups. This survey aimed to describe the basics characteristics and clinical research activity among the Cancer Cooperative Groups (Groupes coopérateurs en oncologie). The second objective was to identify facilitators and barriers to their research activity. A questionnaire was sent to all the clinicians involved in 2014 as investigators in a clinical trial sponsored by one of the ten members of the Cancer Cooperative Groups network. The questions were related to their profile, research activity and the infrastructure existing within their healthcare center to support clinical research and related compliance activities. In total, 366 investigators responded to our survey. The academic clinical trials sponsored by the Cancer Cooperative Groups represented an important part of the research activity of the investigators in France in 2014. These academic groups contributed to the opening of many research sites throughout all regions in France. Factors associated with a higher participation of investigators (more than 10 patients enrolled in a trial over a year) include the existing support of healthcare professionals (more than 2 clinical research associate (CRA) OR=11.16 [3.82-32.6] compared to none) and the practice of their research activity in a University Hospital Center (CHU) rather than a Hospital Center (CH) (OR=2.15 [1.20-3.83]). This study highlighted factors that can strengthen investigator clinical research activities and subsequently improve patient access to evidence-based new cancer therapies in France.


Known occupational carcinogens and their significance.
Although rates of occupational cancer can be excessive in certain industries, less than 5% of all cancers seem attributable to exposure to carcinogens in the workplace. For example, workers in hard-rock mining and the woodworking industries are at increased risk; cigarette smoking has a synergistic effect. There is conclusive evidence of carcinogenicity for fewer than 20 substances, including asbestos, arsenic, chromium, nickel, cadmium, radon, several aromatic hydrocarbons and certain herbicides. Most of the hundreds of organic compounds known to be mutagenic in in-vitro tests have not been shown to be carcinogenic in epidemiologic studies. Both laboratory and epidemiologic approaches, however, can identify probable causes of cancer and permit the application of effective preventive measures. In addition, it is still possible for the alert individual clinician to make the initial discovery of an occupational hazard.


Strong frequency dependence of dynamical coupling between protein and water.
We use molecular dynamics simulations to study thermal energy flow between a green fluorescent protein and surrounding water to unravel the nature of dynamical coupling between biomolecules and their aqueous environment. We find that low-frequency vibrations in protein, which are thought to be critical for the protein function, are strongly coupled with water, whereas intermediate- and high-frequency vibrations are essentially decoupled with water except for those present at the surface of the protein. Our studies shed a new light on the physical mechanism underlying the dynamical slaving of proteins to water.


Can neoadjuvant chemoradiotherapy combined with immunotherapy benefit patients with microsatellite stable locally advanced rectal cancer? a pooled and integration analysis.
To assess the clinical efficacy of neoadjuvant chemoradiotherapy combined with immunotherapy for patients with microsatellite stable (MSS) locally advanced rectal cancer and provide evidence to support clinical decision-making. A systematic search was conducted on the PubMed, Embase, Cochrane Collaboration databases, conference summaries, and Chinese databases for clinical studies that investigated neoadjuvant chemoradiotherapy combined with immunotherapy for the treatment of locally advanced rectal cancer with MSS status. The search spanned from the inception of each database through July 2023. Data from the identified studies were extracted using a pre-designed table, and efficacy outcomes were analyzed. An integrated analysis was conducted using Stata 12.0 software. Eight studies were included, comprising 204 patients with locally advanced MSS rectal cancer who received chemoradiotherapy combined with immunotherapy. The integrated analysis revealed a pathologic complete remission rate of 0.33, a sphincter preservation rate of 0.86, an R0 resection rate of 0.83, a major pathologic remission rate of 0.33, and a clinical complete remission rate of 0.30. Neoadjuvant chemoradiotherapy combined with immunotherapy demonstrates significant short-term efficacy in MSS-type locally advanced rectal cancer, notably enhancing the pathologic complete remission and sphincter preservation rates. This combination is a recommended treatment for patients with MSS-type rectal cancer.


Rapid and efficient pesticide detection via cyclodextrin-promoted energy transfer.
Cyclodextrins facilitate non-covalent fluorescence energy transfer from a variety of pesticides to high quantum-yield fluorophores, resulting in a rapid, sensitive detection scheme for these compounds with detection limits as low as two micromolar. Such a facile detection tool has significant potential applications in agriculture and public health research.


Elevated serum aluminum levels in hemodialysis patients associated with use of electric pumps--Wyoming, 2007.
Aluminum toxicity can cause osteomalacia, anemia, and dementia in hemodialysis patients and has historically been associated with exposure to contaminated water or dialysate preparations or ingestion of aluminum-containing phosphate binders. Since 2002, improvements in water treatment methods and use of non-aluminum-containing phosphate binders have resulted in low prevalence (<1%) of aluminum toxicity among hemodialysis patients. In the United States, reported cases of aluminum toxicosis are rare, and no outbreak has been reported since 1992. This report describes 10 patients treated at a hemodialysis unit in a Wyoming hospital (hospital A) in 2007 who had elevated serum aluminum levels that were detected through routine serum aluminum screening. An investigation was conducted by the Wyoming Department of Health, which determined that the source of exposure was dialysate acid concentrate that became contaminated with aluminum as it passed through two electric drum pumps. The drum pumps had been used to transfer dialysate acid concentrate from 55-gallon storage drums to 1-gallon jugs for use on individual hemodialysis machines. Removal of the pumps from service resulted in a rapid reduction in patient serum aluminum levels. The findings suggest that regular assessment of machine compatibility with dialysate fluid is needed.


Hepatitis B knowledge and vaccination levels in California Hmong youth: implications for liver cancer prevention strategies.
Although chronic infection with hepatitis B virus (HBV) is one of the major risk factors for liver cancer, the level of knowledge about liver cancer risk factors and HBV transmission, as well as vaccination have not been assessed in this population. We interviewed Hmong youth living in Fresno, California about liver cancer risk factors. General knowledge of HBV was common, but knowledge of specific modes of transmission was low. For example, only 49% knew that HBV was transmitted by sexual intercourse. We also observed very low prevalence of HBV vaccination (12%), although a majority reported knowing that shots can prevent disease (68%). Liver cancer prevention and control methods targeted to Hmong youth are needed.


The evaluation of the postoperative course in patients operated due to abdominal aortic aneurysm as urgent or elective procedure.
The patients with the aortic abdominal aneurysm of 55mm in diameter are qualified for surgery. There is open repair (OR) by means of the vascular prosthesis implantation or the less invasive endovascular method by means of the stent graft implantation through femoral arteries incision (EndovascularAorticRepair - EVAR). The aim of the study was the evaluation of the postoperative course in patients operated due to the aortic abdominal aneurysm and the evaluation of the impact of the surgical method on the short-time results. 124 patients operated due to the abdominal aortic aneurysm in Dept of Surgery of 4th Military Hospital in Wroclaw in 2014 were enrolled into the study: 53 patients with OR, 53 patients with EVAR, and 19 patients with a ruptured aneurysm. Mortality was 0% in EVAR and 6% in OR and 39% in a ruptured aneurysm. Time of hospital stay was 5.8 days in EVAR vs 10 days in OR. The stay in ICU was 0% in EVAR vs 13% in OR. Blood transfusion was 9.4% in EVAR vs 66% in OR. Time of postoperative analgesia was 27 h in EVAR vs 76.8 h in OR. Cardio-respiratory decompensation was 1.9% in EVAR vs 7.6% in OR. Renal insufficiency was 2% in EVAR vs 9% in OR. The lower rate of organ complications was in EVAR. The ruptured aneurysm presented the most complicated postoperative course: hospital stay of 11.4 days, ICU stay of 78%, blood transfusion of 100%, painkillers of 136 hours, cardio-respiratory decompensation of 81% and renal insufficiency of 69%. The method of treatment, the conditions of the admission and the type of surgery influenced the postoperative course. The elective EVAR patients presented both the 0% of mortality and the lightest postoperative course. The ruptured abdominal aortic aneurysms operated as an emergency had the most complicated postoperative course.


Distribution and evolution of sequence characteristics in the E. coli genome.
The mean (G + C) composition (51.0%) and standard deviation (+/- 3.8%) of published DNA sequences accounting for 10% of the E. coli genome is in excellent agreement with the principal overall distribution determined by high resolution melting. While differences in base and neighbor characteristics are small and uniform throughout all regions of the genome, it is found that the (G + C) content of sequences varies in segmented fashion within boundaries corresponding to coding (53% G + C) and noncoding (46% G + C) regions; with variances in the latter being six-fold greater than in coding regions. The variance in different regions shows a strong negative dependence on (G + C) content of the region, reflecting the condition that A-T and G-C base pairs are preferred neighbors of A-T and C-G pairs, respectively; with the bias increasing with decreasing (G + C) content. Neighbor analysis indicates the most extreme positive biases occur in AA, TT, GC and CG throughout all regions, but particularly in noncoding regions. Extraordinary numbers of oligomeric strings of (A)n, etc., are the further consequence of this bias. These and other characteristics point to the existence of inherent biases in neighbor frequencies levied during replication or repair, and which reflect, in turn, neighbor influences during mutation. The bias in codon usage noted by Grantham and others is seen here as due, in part, to the adaptation of coding sequences to this microenvironment through selection among synonymous codons so as to preserve inherent neighbor biases.


The predictive accuracy of pre-adoption video review in adoptees from Russian and Eastern European orphanages.
Many internationally adopted children have a pre-adoption video for prospective adoptive parents to review before their commitment to adopt. No published report to date has examined the value of the pre-adoption video evaluation (PreAVE) as a predictor of post-adoption developmental status. The present study was designed to determine whether PreAVE can predict the post-adoption developmental status of internationally adopted children. In this retrospective chart review, children who presented to the Yale International Adoption Clinic between December 1998 and September 2000, and had both a PreAVE and a post-adoption developmental evaluation (PosADE) were selected (N = 20) PreAVE was done using the Denver II and PosADE was done using the Bayley Scales of Infant Development, 2nd edition. The Pearson r coefficient between the two ratings was determined and sensitivity and specificity were calculated. There was a significant correlation between the PreAVE and the PosADEs (r = 0.53, p = 0.01).The sensitivity of PreAVE to detect moderate to severe developmental delay was 43% and the specificity was 85%. Although ratings of development on PreAVE are similar to PosADE, the ability to detect moderate to severe developmental delay by video review is limited.


[A test to evaluate the activity of n-acetyltransferase and catalase in pathologic states of pregnancy].
The activity of N-acetyltransferase (NAT) and catalase was measured in the tissues of placenta, full venous blood and full umbilical cord blood in 141 complicated pregnancies. The control group consisted of 34 physiological pregnancies. The enzymes activity was marked by use of biochemical methods. It has been shown that NAT and catalase is the most active in the group of physiological pregnancies. The decrease of NAT and catalase in venous and umbilical cord blood is correlated with the decrease of the activity these enzymes in placenta.


Steroid metabolism in the brain: From bird watching to molecular biology, a personal journey.
Since Arnold Adolph Berthold established in 1849 the critical role of the testes in the activation of male sexual behavior, intensive research has identified many sophisticated neurochemical and molecular mechanisms mediating this action. Studies in Japanese quail demonstrated the critical role of testosterone action and of testosterone aromatization in the sexually dimorphic medial preoptic nucleus in the activation of male copulatory behavior. The development of an immunohistochemical visualization of brain aromatase in quail then allowed further refinement in the localization of the sites of neuroestrogens production. Testosterone aromatization is required for the activation of both appetitive and consummatory aspects of male sexual behavior. Brain aromatase activity is modulated by steroid-induced changes in the transcription of the corresponding gene but also more rapidly by phosphorylation processes. Sexual interactions with a female also rapidly regulate brain aromatase activity in an anatomically specific manner presumably via the release and action of endogenous glutamate. These rapid changes in estrogen production modulate sexual behavior and in particular its motivational component with latencies ranging between 15 and 30min. Brain estrogens seem to act in a manner akin to a neurotransmitter or at least a neuromodulator. More recently, assays of brain estradiol concentrations in micropunched samples or in dialysis samples obtained from behaviorally active males suggested that aromatase activity measured ex vivo might not be an accurate proxy to the rapid changes in local neuroestrogens production and concentrations. Studies of brain testosterone metabolism are thus not over and will keep scientists busy for a little longer. Elsevier SBN Keynote Address, Montreal.


A SPR and AFM study of the effect of surface heterogeneity on adsorption of proteins.
The effect of chemical heterogeneity of surfaces on the adsorption of proteins was investigated using model surfaces prepared by self-assembly of omega-functionalized alkanethiols on gold substrates. Surface plasmon resonance was used to monitor the adsorption kinetics of bovine serum albumin (BSA) and the morphology of the adsorbed BSA was imaged with tapping mode atomic force microscopy. The experiments show that the morphology of the adsorbed protein layer was altered significantly only when the surface heterogeneity was distributed in a patchwise manner on a nanometer length scale, which is commensurate with the dimension of the protein. In contrast to linear flexible polymers where the initial adsorption rate remained unchanged upon introduction of the chemical heterogeneity, the initial rate for the globular protein changed from the value observed on homogeneous surfaces and was dependent on the heterogeneous distribution of the chemical sites.


Aqueous Boron Removal by Using Electrospun Poly(vinyl alcohol) (PVA) Mats: A Combined Study of IR/Raman Spectroscopy and Computational Chemistry.
We report the use of a novel and efficient method to remove aqueous boron by using electrospun, water-resistant poly(vinyl alcohol) (PVA) mats stabilized in methanol. The removal of the primary aqueous boron species as (B(OH)3), was accomplished by chemical adsorption in reactions with -OH (hydroxyl) groups on the PVA mat surface. The chemical adsorption of B(OH)3 was qualitatively confirmed by the analysis of IR and Raman spectra. The bands, corresponding to the molecular vibration modes of chemically bonded boron in PVA, were identified by using the frequency calculation from the computational chemistry for the first time. The adsorption capacities of PVA mats for aqueous boron were then quantitated at a low boron concentration (range: 0.0010 to 0.0025 g of aqueous boron per g of PVA mats) by the Carmine method. The PVA mats were prepared by a well-established electrospinning technique, which make these substrates promising potential candidates for use as boron-selective sorbent media in applications such as reverse osmosis desalination processes.


Evaluation of results of conservative therapy in patients with transient osteoporosis of hip.
The present study aimed to review the general characteristics of 18 cases diagnosed with transient osteoporosis of the hip (TOH) in our hospital within a 3-year period and to present their follow-up results after conservative treatment. A retrospective evaluation was made of the treatment and results of follow-up of TOH cases using physical examination and laboratory findings, hip radiographs and magnetic resonance imaging (MRI) and Harris Hip Scores (HHS). The mean duration of complaints of 6 females (mean age, 34.3±4.3 years) and 12 males (mean age, 40.7±10.5 years) was 6.1±2.7 weeks before the treatment. Three female patients had a history of giving birth by cesarean delivery. None of the patients had any history of trauma. MRI revealed increased intensity in T2 sequences and decreased intensity in T1 sequences in the proximal aspect of the femur. None of the patients had subchondral collapse or intra-articular effusion. For 3 female patients who were breastfeeding, no medical therapy was given, but only hyperbaric oxygen (HBO) therapy and forearm crutches. As standard management, the other patients were prevented from weight-bearing with the use of forearm crutches and medical therapy of diclofenac sodium, acetylsalicylic acid, and risedronate sodium was administered and additional HBO therapy. Clinical and radiological improvements were observed in all patients. None of the patients had avascular necrosis (AVN) of the femoral head. There was no record of therapy-related complications. While HHS was 55.6±7.8 before the treatment, it increased to 88.8±5.8 in the 3rd month and to 96.0±1.8 in the 6th month after the treatment. This change in score over time was found to be significant.


Construction of robust enzyme nanocapsules for effective organophosphate decontamination, detoxification, and protection.
Nanocapsules of organophosphorous hydrolase with enhanced enzyme activity and stability are prepared via in situ polymerization, providing a novel class of nanoparticles for the decontamination and detoxification of organophosphates such as chemical warfare agents and pesticides. Using the nanocapsules as building blocks, bioactive nanocomposites are also fabricated, enabling their use for organophosphate protection.


New mechanistic insights into the RAS-SIN1 interaction at the membrane.
Stress-activated MAP kinase-interacting protein 1 (SIN1) is a central member of the mTORC2 complex that contains an N-terminal domain (NTD), a conserved region in the middle (CRIM), a RAS-binding domain (RBD), and a pleckstrin homology domain. Recent studies provided valuable structural and functional insights into the interactions of SIN1 and the RAS-binding domain of RAS proteins. However, the mechanism for a reciprocal interaction of the RBD-PH tandem with RAS proteins and the membrane as an upstream event to spatiotemporal mTORC2 regulation is not clear. The biochemical assays in this study led to the following results: 1) all classical RAS paralogs, including HRAS, KRAS4A, KRAS4B, and NRAS, can bind to SIN1-RBD in biophysical and SIN1 full length (FL) in cell biology experiments; 2) the SIN1-PH domain modulates interactions with various types of membrane phosphoinositides and constantly maintains a pool of SIN1 at the membrane; and 3) a KRAS4A-dependent decrease in membrane binding of the SIN1-RBD-PH tandem was observed, suggesting for the first time a mechanistic influence of KRAS4A on SIN1 membrane association. Our study strengthens the current mechanistic understanding of SIN1-RAS interaction and suggests membrane interaction as a key event in the control of mTORC2-dependent and mTORC2-independent SIN1 function.


Needle-free injection of DNA vaccines: a brief overview and methodology.
The development of needle-free injection originally stemmed from a general apprehension of needle injections, disease transmission by accidental needle-sticks, and the need for effective mass immunization. Naked DNA vaccines, as attractive and universal as they appear, have not produced robust immune responses in test systems. However, proof of principle for DNA vaccines has been validated with a number of vaccine candidates in a variety of test systems, and the concept of DNA vaccines as a generic platform for vaccines still remains viable and attractive. Many avenues are being explored to enhance the immunogenicity of DNA vaccines. The easiest and most straightforward approach that can be quickly transitioned to a clinical trial setting is vaccine delivery by a needle-free jet injector. This approach has shown much potential in a number of cases and should become the lead method for enhancing DNA vaccines. This approach requires no additional development, and with an expanding market and willingness from jet injector manufacturers to produce prefilled syringes, the technique should become feasible for larger phase II/phase III trials.


The R1162 relaxase/primase contains two, type IV transport signals that require the small plasmid protein MobB.
The relaxase of the plasmid R1162 is a large protein essential for conjugative transfer and containing two different and physically separate catalytic activities. The N-terminal half cleaves one of the DNA strands at the origin of transfer (oriT) and becomes covalently linked to the 5' terminal phosphate; the C-terminal half is a primase essential for initiation of plasmid vegetative replication. We show here that the two parts of the protein are independently transported by the type IV pathway. Part of the domain containing the catalytic activity, as well as an adjacent region, is required in each case, but the required regions do not physically overlap. Both transport systems contribute to the overall frequency of conjugative transfer. MobB is a small protein, encoded within mobA but in a different reading frame, that stabilizes the relaxase at oriT. MobB is required for efficient type IV transport of both the complete relaxase and its two, separate functional halves. MobB inserts into the membrane and could thus stabilize the association between the relaxase and the type IV transfer apparatus.


Technical Note: Feasibility study of titanium markers in choroidal melanoma localization for proton beam radiation therapy.
The purpose of this study is to explore the feasibility of the use of titanium fiducial markers to minimize the metallic artifact seen with tantalum markers which causes significant distortion on postoperative orbital CT scans. We designed and constructed the titanium markers in the shop of Crocker Nuclear Laboratory, UC Davis, CA. The markers were placed on an eyeball phantom. The eyeball was inserted into the Rando phantom in the orbital space. The Rando phantom was imaged with coplanar x rays on Nucletron simulator at UCSF, on digital panel on the eye beam line at CNL eye treatment facility and on CT scanner at UCSF. The titanium markers can be clearly seen on the hard copy of x rays and on digital panel. The CT scan of an orbit using tantalum markers on the right eye and titanium markers on the left eye shows the metal artifact from tantalum markers. Titanium markers show very little distortion on CT images. The present study describes these markers and their relative benefit in comparison with tantalum marker, which has been used for localizing ocular tumor for decades.


CKD Due to a Novel Mitochondrial DNA Mutation: A Case Report.
In human kidney disease, mitochondrial ultrastructural damage has long been recognized. Although the extent to which such mitochondrial changes contribute to human kidney disease is uncertain, experimental studies clearly demonstrate that mitochondrial damage can instigate pathogenetic processes that drive ongoing kidney disease. Clinical credence for this experimentally based hypothesis is provided by the development of kidney disease in patients with primary mitochondrial disorders. In this regard, substantial interest surrounds the occurrence of kidney disease in primary mitochondrial cytopathies, a heterogeneous group of conditions in which mutations in mitochondrial DNA (mtDNA) or nuclear DNA impair the functionality of components of the mitochondrial respiratory chain. We describe a novel mtDNA mutation in a patient who developed chronic kidney disease. The patient exhibited mitochondrial abnormalities in both muscle and kidney, chronic tubulointerstitial changes, and recurrent episodes of rhabdomyolysis. We outline mechanisms that may underlie the occurrence of chronic kidney disease in the setting of this novel mtDNA mutation. We also underscore the need to consider in relevant kidney diseases the presence of an underlying mitochondrial cytopathy because the latter more commonly exists than is generally recognized.


The association of environmental, individual factors, and dopamine pathway gene variation with smoking cessation.
This study aimed to examine whether dopamine (DA) pathway gene variation were associated with smoking cessation, and compare the relative importance of infulence factors on smoking cessation. Participants were recruited from 17 villages of Shandong Province, China. Twenty-five single nucleotide polymorphisms in 8 DA pathway genes were genotyped. Weighted gene score of each gene was used to analyze the whole gene effect. Logistic regression was used to calculate odds ratios (OR) of the total gene score for smoking cessation. Dominance analysis was employed to compare the relative importance of individual, heaviness of smoking, psychological and genetic factors on smoking cessation. 415 successful spontaneous smoking quitters served as the cases, and 404 unsuccessful quitters served as the controls. A significant negative association of total DA pathway gene score and smoking cessation was observed (p < 0.001, OR: 0.25, 95% CI 0.16-0.38). Dominance analysis showed that the most important predictor for smoking cessation was heaviness of smoking score (42%), following by individual (40%), genetic (10%) and psychological score (8%). In conclusion, although the DA pathway gene variation was significantly associated with successful smoking cessation, heaviness of smoking and individual factors had bigger effect than genetic factors on smoking cessation.


Mechanical Properties of Composite Hydrogels for Tissue Engineering.
Tissue engineering provides solutions that require medicine to restore damaged tissues or even complete organs. This discipline combines biologically active scaffolds, cells and molecules; being the addition of nanoparticles into the scaffolds, one of the techniques that is attracting more interest these days. In this work, Hydroxyapatite Nanorods (HA) were added to the network of Gelatin hydrogel (GE), and the particular properties resulting from their interaction were studied. Specifically, viscoelastic properties were characterized as a function of gel and nanoparticle concentration, varying ratios and temperatures. Oscillatory Time Sweeps (OTS) provided the necessary information about how the timeresolved material property/structure alteration. A wide variety of Continuous Flow Tests and Frequency Sweeps were used to describe the mechanical properties of the material, proving that the presence of nanoparticles led to a reinforcement of the gel network, mechanical stiffness and strength. The thixotropic nature of the gels was also evaluated and the most common theoretical models were described and commented. The attributes inferred from the data, showed a material that can allow the natural growth of bone tissue whilst withstanding properly the mechanical efforts; resulting in a material with an outstanding suitability to be used in regenerative medicine.


Philosophical, ethical, and legal aspects of resuscitation medicine. I. Deferred consent and justification of resuscitation research.
Informed prospective consent for clinical resuscitation research may not be possible. Deferred consent is an untenable notion. Consent to continue in research cannot be used to support a claim that there was, or would have been, consent to the initiation of research. The conditions for the justifiability of resuscitation research without informed consent are: a) patient is comatose; b) lifesaving treatment must be given immediately; c) given all available evidence, there is reason to believe that the probability of death or severe deficit with experimental or control therapy is not greater than the probability of death or severe deficit on usual therapy; d) given all available evidence, there is reason to believe that the probability of normal or near-normal outcome is greater on experimental or control therapy than on usual therapy; and e) the study can provide evidence on whether there is a significant difference between experimental and control therapies in the incidence of normal or near-normal survival.


Is event-driven PrEP dosing for HIV as effective as daily dosing?
PROBABLY, although there are no head-to-head trials comparing the 2 dosing regimens. Event-driven pre-exposure prophylaxis (PrEP) dosing reduces HIV conversion by 86% compared to placebo (strength of recommendation [SOR]: B, large randomized controlled trial [RCT]). Daily PrEP reduces HIV conversion by 44% to 86% (SOR: B, based on open-label RCTs).Event-driven PrEP regimens may be associated with lower adherence when compared with daily PrEP regimens (average of 70% for event-driven PrEP vs average of 92% for daily PrEP) (SOR: B, based on open-label and cohort trials). Event-driven PrEP regimens have lower medication costs, and they are associated with no difference in the rate of sexually transmitted infections (STIs) (SOR: B, based on prospective cohort studies). Patients may prefer them to daily regimens (75% choose event driven PrEP vs 25% choose daily PrEP) (SOR: BB, based on the preponderance of prospective cohort studies with conflicting results).


[Chronic fibroplastic leptomeningitis of the spinal cord and cauda equina].
Chronic (seldom subacute) low-grade spinal leptomeningitis, cystic and adhesive in natura, is a clinicopathologic condition known by several names in medical literature (arachnoiditis, arachnoditis adhesiva circumscripta, a.s.o.). The cystic structures are not cysts in the true sense of the word. They are in reality collections of cerebrospinal fluid walled off by meningeal adhesions. The extent of the leptomeningitis varies from a well-localized lesion to a diffused process involving the entire cereprospinal axis. In some cases the chronic proliferative changes lead to calcification and ossification of the leptomeninx. As well the circumscribed adhesive as the cystic form can produce a spinal cord compression syndrome similar to a tumor or a hydro-syringomyelia. Progressive paraparesis with difficulties of bladder and bowel function may nevertheless be arrested, or spontaneous remission may occur, perhaps due to temporary improvement of the local circulation of spinal fluid. An almost typical sciatic syndrome can be occasionally associated with a thickening of the leptomeninx and cystic spinal fluid collection in the region of the cauda equina. The lumbar adhesive and cystic form is as a rule a more benign disease then leptomeningitis occurring at thoracic or cervical levels. The etiological factors are trauma, spinal anesthesia, myelography, blood in the subarachnoid space, previous operations and infections. When the origin of the illness remains unidentified, low grade bacterial or viral infections can be presumed. We operated 2 patients with circumscribed severe leptomeningitis several segments far away from an intradural meningeoma. Such illness is uncommon, but not very rare. From 1970 until the end of 1986 we have carried out 33 laminectomies on 26 patients because of spinal leptomeningitis among 603 patients operated because of spinal cord compression (4.31%). Our cases are presented and literature is discussed. The dilemma what we have to do with a patient with symptomatic spinal leptomeningitis is open: the microsurgery can help the patient significantly, even if complete recovery is rare. In view of the extreme variety of these lesions a circumspect, sometime skeptical analysis of each patient must precede decision about surgery. We try to give some indications for microsurgery.


Colopathy associated with the systemic use of nonsteroidal antiinflammatory medications. An underestimated entity.
Adverse effects of NSAIDs (nonsteroidal antiinflammatory drugs) on the upper gastrointestinal tract and small intestine are well described. Evidence is also accumulating that implicate NSAIDs in inducing and exacerbating damage in the distal gastrointestinal tract. In this article we describe eight cases of colonic inflammation associated with nonsteroidal antiinflammatory drug administration; our aim is to stress the importance of an underestimated entity by clinicians. Over a five-year period at two clinics, eight cases of NSAID-colopathy have been diagnosed. Crohn's disease, ulcerative and infections colitis have been excluded from this analysis. In all these subjects a careful drug history has been taken in a prospective manner and colonic inflammation appeared to be directly related to NSAID administration. There was a time interval (mean: 20 months) between initiation of treatment with NSAID and presentation with diarrhea, rectal hemorrhage and tenesmus. A correct diagnosis of colopathy associated with NSAIDs administration was made on careful drug history, pathological findings, stool cultures and biochemical changes which were insignificant, in contrast to the protracted troublesome symptoms. Resolution of symptoms was observed on discontinuation of NSAID medication. Our report is further evidence that NSAIDs administration is associated with significant mucosal injury in the distal gastrointestinal tract, despite is underestimated by most physicians.


Attachment and psychopathology in a community sample.
The Structured Clinical Interview for DSM-III-R (SCID-I) and the Adult Attachment Interview (AAI) were administered to 60 women participating in a study (n=226) of mother-child interaction. These women were not referred to the study for psychiatric care. The 60 women interviewed with the AAI were selected from the first 190 women who completed the SCID-I, so that 30 received a diagnosis and 30 did not. Analyses indicated that psychopathology diagnoses were associated significantly with mental representations of attachment classified in the AAI. The non-autonomous groups had increased likelihood of SCID diagnosis, compared to the autonomous group. While 32% of women with autonomous AAI transcripts received SCID diagnoses, 63% of women with Dismissing, 100% of woman with Preoccupied, and 65% of women with Unresolved transcripts received diagnoses. Secondary analyses indicated that Dismissing classifications were associated with Axis I diagnoses and Preoccupied classifications with affective disorders. Of note was that among women with Unresolved classifications, underlying secure attachment was associated with low risk of psychopathology, while underlying anxious attachment was associated with elevated risk of diagnosis. These findings support the premise from attachment theory that early relationships affect patterns of interpersonal expectations and behavior and affect regulation.


Can Death Cafés resuscitate morale in hospitals?
Death Cafés are non-profit social franchises that arise spontaneously in communities to serve as informal forums for discussing death. There is a great need within the medical community for the kind of conversation that Death Cafés foster: open, unstructured, spontaneous, genuine and interdisciplinary dialogue. Burnout in healthcare, with symptoms of exhaustion, depersonalisation and decreased efficacy, is a global crisis, with alarming estimates suggesting one in three practicing physicians experience burnout. While open-forum community-based Death Cafés exist widely, there appears to be no evidence in the literature to suggest that healthcare settings have adapted this model for fostering debriefings among hospital employees. We have started hospital-based Death Cafés in a large, public, urban-centre, Level I Trauma centre in the Gulf South in an effort to study healthcare worker burnout. In this brief commentary, we introduce the concept of hospital-based Death Cafés as distinct from community-based Death Cafés. From our experience, hospital-based Death Cafés are easy to implement, inexpensive, require little planning and yet offer tremendous reward to participants. Should the phenomenon of Death Cafés take off in hospitals as it has in communities internationally, we propose that this intervention be studied for its effect on healthcare worker burnout.


Evaluation of the body adiposity index in a Caucasian population: the Hordaland health study.
In this study, we compared the relationships of body mass index (BMI) and body adiposity index (BAI) with body fat percentage (BF%) in a Caucasian, European population. BF% was measured by dual-energy x-ray absorptiometry in a population-based cross-sectional study of 5,193 middle-aged (47-49 years) and elderly (71-74 years) men and women from the Hordaland Health Study in western Norway from 1997 to 1999. In the total population, the correlation between BAI and BF% was stronger (r = 0.78) than the correlation between BMI and BF% (r = 0.56) with similar results in the middle-aged and elderly groups. However, in men and women separately, BMI was a better correlate of BF% (for men, r = 0.76; for women, r = 0.81) than was BAI (for men, r = 0.57; for women, r = 0.72). BMI was also a better correlate of BF% than was BAI assessed by partial correlations adjusted for sex (for BMI-BF%, r = 0.79; for BAI-BF%, r = 0.67). Bland-Altman plots and BF%-stratified analyses showed that BAI tended to overestimate BF% in lean subjects and to underestimate it in those with higher proportions of body fat, but that it predicted BF% well for those whose BMI was in a normal range. At the individual level and in population studies adjusted for sex, BMI outperforms BAI as a predictor of BF%.


Endothelin-1 decreases CD36 protein expression in vascular smooth muscle cells.
Recent studies have shown that CD36 plays important roles as a major scavenger receptor for oxidized low-density lipoproteins and as a crucial transporter for long-chain fatty acids. CD36 deficiency might be associated with insulin resistance and abnormal dynamics of long-chain fatty acids. Endothelin-1 (ET-1), which is synthesized and secreted by vascular endothelial cells, is the most potent endogenous vasoconstrictor known and also stimulates the proliferation of vascular smooth muscle cells (VSMCs) and thus is believed to play an important role in the development of various circulatory disorders, including hypertension and atherosclerosis. The aim of the present study was to investigate the regulatory effect of ET-1 on CD36 expression in cultured VSMCs. VSMCs were treated for different times (0-24 h) with a fixed concentration (100 nM) of ET-1 or with different concentrations (0-100 nM) for a fixed time (24 h); then CD36 expression was determined using Western blots. CD36 expression was significantly decreased by ET in a time- and dose-dependent manner. This inhibitory effect was prevented by the ET(A) receptor antagonist BQ-610 (10 microM) but not the ET(B) receptor antagonist BQ-788 (10 microM). To further explore the underlying mechanisms of ET-1 action, we examined the involvement of the tyrosine kinase-mediated and MAPK-mediated pathways. The inhibitory effect of ET-1 on CD36 protein expression was blocked by inhibition of tyrosine kinase activation by use of genistein (100 microM) and by the ERK inhibitor PD-98059 (75 microM) but not by the p38 MAPK inhibitor SB-203580 (20 microM). In conclusion, we have demonstrated that ET-1, acting via the ET(A) receptor, suppresses CD36 protein expression in VSMCs by activation of the tyrosine kinase and ERK pathways.